Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Boehringer Ingelheim | INDUSTRY |
Not provided
Not provided
Not provided
Double-blind, parallel arm, randomized controlled trial, in which non-lactating women with recent GDM who are between 6 to 36 months postpartum to be randomized to either empagliflozin 10 mg daily or matching placebo. The duration of treatment will be 48-weeks. Beta-cell function will be assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), measured on oral glucose tolerance test (OGTT) at baseline, 24-weeks, 48-weeks, and after a 4-week washout.
Gestational diabetes mellitus (GDM), defined as glucose intolerance of varying severity with first onset and recognition in pregnancy, identifies a population of women who are at high risk for the future development of type 2 diabetes (T2DM). This risk of T2DM is mediated by the progressive deterioration of insulin secretion by the pancreatic beta-cells in the years after delivery, a pathologic process that current anti-diabetic therapies have not been shown to modify. Importantly, since very mild glycemia has deleterious but reversible effects on insulin secretion ("glucotoxicity"), the beta-cell dysfunction of women with recent GDM should have a prominent reversible component that potentially could be mitigated through the elimination of glucotoxicity. In this context, the sodium glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin is a novel anti-diabetic therapy that specifically alleviates glucotoxicity and thus may be able to preserve beta-cell function. Coupled with its capacity to induce weight loss with low risk of hypoglycemia, empagliflozin could be an ideal therapy for diabetes prevention in women with recent GDM. Specifically, by eliminating glucotoxicity, SGLT-2 inhibition could enable the preservation of beta-cell function and thereby prevent the development of incident T2DM in this high-risk population. Thus, a double-blind, parallel arm, randomized controlled trial, in which non-lactating women with recent GDM who are between 6 to 36 months postpartum to be randomized to either empagliflozin 10 mg daily or matching placebo is proposed. The duration of treatment will be 48-weeks. Beta-cell function will be assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), measured on oral glucose tolerance test (OGTT) at baseline, 24-weeks, 48-weeks, and after a 4-week washout.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Empagliflozin | Experimental | Empagliflozin 10 mg PO daily |
|
| Placebo | Placebo Comparator | Matched placebo PO daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin 10 MG | Drug | Empagliflozin 10 mg PO daily |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline-adjusted ISSI-2 at 48-weeks | The primary outcome will be measured by ISSI-2. ISSI-2 is a validated OGTT-derived measure of beta-cell function analogous to the disposition index obtained from the intravenous glucose tolerance test. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve (AUCins) to the area-under-the-glucose curve (AUCgluc) and (ii) insulin sensitivity measured by the Matsuda index. | 48-weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Glucose tolerance status at 48-weeks | Prevalence of dysglycemia on the OGTT at this visit. | 48-weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline-adjusted ΔISR0-120/Δgluc0-120 × Matsuda index at 48 weeks | and insulinogenic index/HOMA-IR. | 48-weeks |
| Baseline-adjusted insulinogenic index/HOMA-IR at 48-weeks | Beta-cell function assessed by ΔISR0-120/Δgluc0-120 × Matsuda index at 48-weeks |
Inclusion Criteria:
Exclusion Criteria:
Women with history of gestational diabetes
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Caroline kramer, MD PhD | MOUNT SINAI HOSPITAL | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Leadership Sinai Centre foe Diabetes - Mount Sinai Hospital | Toronto | Ontario | M5T 3L9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40964955 | Derived | Murugavel S, Retnakaran R, Feig DS, Zinman B, Kramer CK. Empagliflozin for the preservation of beta-cell function in women with recent gestational diabetes: A randomized placebo-controlled trial. Diabetes Obes Metab. 2025 Dec;27(12):7408-7415. doi: 10.1111/dom.70146. Epub 2025 Sep 18. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D016640 | Diabetes, Gestational |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D003920 | Diabetes Mellitus |
Not provided
Not provided
| ID | Term |
|---|---|
| C570240 | empagliflozin |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo oral capsule |
| Drug |
Placebo PO daily |
|
| 48-weeks |
| Body mass index at 48-weeks | 48-weeks |
| Insulin sensitivity at 48 weeks. | Insulin sensitivity will be measured by Matsuda index on OGTT | 48-weeks |
| Central abdominal fat mass at 48 weeks | Central abdominal fat mass will be measured by DXA assessment at L2-L4 | 48-weeks |
| Quality of life at 48 weeks | Quality of life will be assessed annually by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). | 48-weeks |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |